Received: 27 November 2018 | Revised: 11 January 2019
DOI: 10.1002/jcb.28790
RESEARCH ARTICLE
Cytokine fibroblast growth factor 10 (FGF10)
polymorphisms are associated with risk of myopia
in young children
Wei Sun1 | Yinan Li2 | Jing Li1
Zhenyu Zhang1 | Jianfang Kang3
1
Department of Ophthalmology,
Guangdong Women And Children
Hospital, Guangzhou, Guangdong, China
2
Department of Anesthesiology, The First
Affiliated Hospital of Guangzhou Medcial
University, Guangzhou, Guangdong,
China
3
Department of Ophthalmology, Huai’an
Second People's Hospital, The Affiliated
Huai’an Hospital of Xuzhou Medical
University, Huai’an, Jiangsu, China
Correspondence
Jianfang Kang, Department of
Ophthalmology, Huai’an Second People's
Hospital, The Affiliated Huai’an Hospital
of Xuzhou Medical University, Huai’an
223002, Jiangsu, China.
Email: kangjf2010@aliyun.com
Xuelin Huang, Department of
Ophthalmology, Guangdong Women And
Children Hospital, Guangzhou 511400,
Guangdong, China.
Email: huangxl1@aliyun.com
Wei Sun and Yinan Li contributed equally to this work.
J Cell Biochem. 2019;1-7.
| Accepted: 25 January 2019
| Xiaoming Zhang1 | Qingyang Feng1 |
| Xuelin Huang1
Abstract
Myopia has become a major public health issue worldwide. Identification of
genetic loci related to myopia in young children may advance our knowledge of
the pathogenesis of myopia. Fibroblast growth factor 10 (FGF10) plays essential
roles for the development of myopia through modulating extracellular matrix‐
associated genes. Studies revealed that genetic variants of FGF10 were
associated with extreme myopia in adults. However, their associations with
susceptibility of myopia in young children, which are less affected by
confounding factors and more suitable for studying genetic factors of myopia,
have not been explored. In the current study, we evaluated 13 tagSNPs that
captured 100% of genetic variation in the FGF10 gene region for their
associations with myopia in a large Chinese case‐control study with 900 myopia
children and 900 nonmyopia children. We found rs2973644 was significantly
associated with increased risk of myopia (odds ratio [OR]: 1.26; 95% confidence
intervals [CI]: 1.06‐1.49; P = 0.009). furthermore, rs339501 (OR: 1.73; 95% CI:
1.18‐2.53; P = 0.005), rs2973644 (OR: 1.57; 95% CI: 1.13‐2.19; P = 0.007), and
rs79002828 (OR: 1.83; 95% CI: 1.20‐2.77; P = 0.005) were significantly associated
with increased risk of high myopia in young children. Functional assessment of
rs2973644 by luciferase assays revealed the risk G allele causes a higher
expression level of FGF10 than the protective A allele. Our results do support
that genetic variants of cytokine FGF10 are associated with susceptibility of
myopia (as well as high myopia) in young children and further exploration are
needed for myopia in children.
KEYWORDS
fibroblast growth factor 10, genetic, myopia, polymorphism, young children
1 | INTRODUCTION
Myopia, with its prevalence increasing rapidly recently,
has become a major public health issue worldwide.1-7 It is
a major cause of reduced vision and blindness among
wileyonlinelibrary.com/journal/jcb © 2019 Wiley Periodicals, Inc. | 1
2 | SUN ET AL.

children and adolescents.8 It was reported that myopia is 2 | METHODS

especially common in urban regions of Asian countries,
such as Singapore, Taiwan, Japan, and Hong Kong, 2.1 | Study subjects
where 60% to 80% of young adults are myopic.9 Although
All processes used in the study followed the tenets of the
the exact pathogenesis of myopia remains unraveled,
Declaration of Helsinki and written informed consent was
previous studies revealed environmental factors, like age,
obtained from all subjects and their parents. The protocol
sex, education levels, blood vitamin D status, time spent
was approved by the Human Research Ethics Committee at
outdoors, and time using electronic equipment could
the two hospitals (Guangdong Women and Children
contribute to the development of myopia.10-12 Besides,
Hospital and Huai’an Second People’s Hospital). Totally
genetic factors also play a major role in the occurrence of
included in the current study were 900 myopia children and
myopia.13-15 According to the results of a twin study, the
900 nonmyopia children, which were recruited in Guang-
estimated heritability for myopia was as high as 91%.16 To
dong Women and Children Hospital and Huai’an Second
present, family linkage analysis, genome‐wide associa-
People’s Hospital from 2010. Myopia was defined as mean
tion studies, next‐generation‐sequencing studies, together
spherical equivalent (the sum of spherical error and half of
with candidate gene studies have identified more than
the cylindrical error) of both eyes ≤−0.5 D, which were
200 genes and loci for myopia.17 However, a large
widely used and validated reliability in young individuals.27
proportion of the genetic heritability remains unclear,
The diagnosis for high myopia required the spherical
and need to be explored.
equivalent ≤−6.0 D in at least one eye. Participants with a
Previously, two studies revealed that genetic poly-
previous history of ocular surgery or trauma, ophthalmic
morphisms in fibroblast growth factor 10 (FGF10) were
disease predisposed to myopia, and genetic or systemic
associated with extreme myopia (≤−10 diopters [D]) in
disorder associated with myopia were excluded. Children
adults.18,19 FGF10 is an epithelial‐mesenchymal signaling
with LogMAR visual acuity ≤0.1, no glasses or ophthalmic
molecule.20 FGF10 could modulate extracellular matrix‐
history were classified as nonmyopic.28 The control group
associated genes, which are essential for the development
was matched with cases in both sex and age parameters. All
of myopia.19 Defect in FGF10 could also lead to the
participants had similar social backgrounds and resided in
development and differentiation of multiple ocular
the same urban area. Up to 10 mL of venous blood was
tissues, and cause eye diseases, like lacrimal and salivary
collected from each participant.
gland syndrome, failure of eyelid fusion, and myo-
pia.13,20-26 Myopia in young children, which increased
dramatically, is urgent from a public health perspective. 2.2 | TagSNPs selection, DNA
Considering the important role of FGF10 gene, whether extraction, and genotyping
genetic polymorphisms in FGF10 were associated with
myopia in young children are worthy to be explored. In Thirteen tagSNPs covering the FGF10 region from the gene
the current study, 13 tagSNPs covering the FGF10 region were selected from 1000 genome CHB data (phase 3, minor
from the gene were selected from 1000 genome CHB data allele frequency ≥5%, pairwise r2 ≥ 0.8) using the Haploview
(Figure 1), and evaluated in a case‐control study with 900 4.2 software. Genomic DNA was extracted from peripheral
myopia children and 900 nonmyopia children. blood samples using the QIAamp DNA Blood Mini Kit
(Qiagen, Hilden, Germany). Genotyping was performed by
TaqMan assays (Applied Biosystems, Foster City, CA)
according to the manufacturer’s instructions. A randomly
selected set of 45 (5%) samples was tested in duplicate by
different persons, and the results were 100% concordant.

2.3 | Cell line, construction of reporter

plasmids, transient transfections, and
luciferase assays
The HRPE‐19 (also known as ARPE‐19) cell line was
purchased from the Cell Bank of Type Culture Collection of
the Chinese Academy of Sciences Shanghai Institute of
Biochemistry and Cell Biology. The reporter vector was
FIGURE 1 TagSNPs covering the FGF10 gene. FGF10, generated encoding the 400‐bp FGF10 intron region flanking
fibroblast growth factor 10 rs2973644[A] or rs2973644[G]. Desired DNA fragments were
SUN ET AL. | 3

inserted into luciferase reporter vector pGL3‐Basic (Promega,
Madison, WI). The inserts were positioned in sense
orientation relative to the luciferase coding sequence. The
construct containing A allele of rs339501 was confirmed by
DNA sequencing. To establish the construct carrying the
rs2973644G allele, the site‐directed mutagenesis experiments
were conducted by overlap extension PCR. Then 500 ng of
reporter plasmid was cotransfected into HRPE‐19 cells using
Lipofectamine 2000 (Invitrogen, Carlsbad, CA). Cells were
collected 24 hours after transfection, and Renilla luciferase
activity was detected and used to normalize firefly luciferase
activity.
2.4 | Statistical analysis
The Hardy‐Weinberg equilibrium (HWE) test was per-
formed for both patients and healthy controls by a
goodness‐of‐fit χ2 test. For the intergroup comparison
between the cases and the controls or between the
subgroups of the patients stratified according to clinical
features, the Student t test and the χ2 test were used to
analyze the continuous date and the categorical data,
respectively. Odds ratios (ORs) and 95% confidence
intervals (CIs) were calculated to estimate the association
between FGF10 polymorphisms and the risk of myopia. A
P < 0.05 was used as statistical significance. SPSS version
22.0 (SPSS Inc, Chicago, IL) was used for the data analysis.
3 | RESULTS
3.1 | Characteristics of study subjects
As shown in Table 1, we totally included 900 myopia
children and 900 nonmyopia children in the current
study. Among the 900 myopia children, 99 children
were determined as high myopia. Basic characteristics
of our current subjects are shown in Table 1. Age, sex,
and body mass index were comparable among all
groups, while myopia and high myopia have longer
time using electronic equipment, shorter time spent
outdoors, as well as more parental myopia than
nonmyopia in turn.
3.2 | Hardy‐Weinberg equilibrium
As shown in Table 2, all the SNPs (rs339501, rs2973644,
rs17234135, rs17234079, rs138552923, rs79002828, rs2128433,
rs78139768, rs10055386, rs1482674, rs1839090, rs2290070,
rs78454549) analyzed were in HWE in nonmyopia controls,
which indicated that the sampled subjects were representa-
tive of the population without any deviation of genotype
frequencies (P > 0.05).
3.3 | Genetic association study for
FGF10 polymorphisms with myopia in
young children
The results of genotypic frequency analysis for each
tagSNPs selected are as shown in Table 2. We found the
only rs2973644 was significantly associated with in-
creased risk of myopia (OR: 1.26; 95% CI: 1.06‐1.49;
P = 0.009). The AG genotype was associated with a 1.25‐
fold increased risk (95% CI = 1.00‐1.57; P = 0.048) of
myopia as compared with the AA genotype, while the GG
genotype conferred a 1.52‐fold increased risk of myopia
compared with the AA genotype (95% CI = 1.02‐2.27;
P = 0.040).

T A B L E 1 Characteristics of study participants

No myopia children
(n = 900) Myopia children (900) High myopia children (99)
Age (y) 11 (2.4) 11 (2.7) 11 (2.2)
Sex
Boys 468 (52.0%) 463 (51.4%) 54 (54.5%)
Girls 432 (48.0%) 437(48.6%) 45 (45.5%)
2
BMI (kg/m ) 15.2 (3.4) 15.4 (3.1) 15.3 (3.0)
Time spent outdoors (h/d) 1.66 (1.03) 1.37 (0.87) 1.07 (0.84)
Time using electronic equipment (h/d) 1.36 (0.87) 1.79 (0.99) 2.10 (1.12)
Parental myopia
Yes 185 (20.6%) 220 (24.4%) 34 (33.3%)
No 715 (79.4%) 680 (75.6%) 65 (66.7%)
Abbreviation: BMI, body mass index.
Values are means (standard deviation) or percentages (absolute numbers)
4 | SUN ET AL.

T A B L E 2 The associations between tagSNP of FGF10 and myopia

Genotype Myopia Controls Adjusted OR (95% CI)* P value

rs339501
AA 670 681 1.00 (reference)
AG 215 209 1.09 (0.74‐1.61) 0.674
GG 15 10 1.59 (0.69‐3.66) 0.279
G vs A 1.12 (0.85‐1.48) 0.408
rs2973644
AA 472 520 1.00 (reference)
AG 359 328 1.25 (1.00‐1.57) 0.048
GG 69 52 1.52 (1.02‐2.27) 0.040
G vs A 1.26 (1.06‐1.49) 0.009
rs17234135
CC 769 765 1.00 (reference)
CT 125 127 1.02 (0.82‐1.27) 0.871
TT 6 8 0.78 (0.32‐1.86) 0.570
T vs C 0.99 (0.96‐1.03) 0.695
rs17234079
CC 781 792 1.00 (reference)
CT 114 105 1.15 (0.78‐1.67) 0.484
TT 5 3 1.76 (0.41‐7.52) 0.447
T vs C 1.17 (0.84‐1.64) 0.358
rs138552923
CC 772 784 1.00 (reference)
CT 123 110 1.18 (0.84‐1.67) 0.343
TT 5 6 0.88 (0.37‐2.1) 0.773
T vs C 1.14 (0.81‐1.61) 0.454
rs79002828
AA 713 737 1.00 (reference)
AG 170 154 1.19 (0.88‐1.6) 0.260
GG 13 9 1.55 (0.64‐3.78) 0.333
G vs A 1.21 (0.93‐1.57) 0.152
rs2128433
AA 409 405 1.00 (reference)
AT 336 335 1.03 (0.41‐2.6) 0.945
TT 55 50 1.13 (0.64‐1.99) 0.666
T vs G 1.06 (0.65‐1.72) 0.821
rs78139768
AA 708 715 1.00 (reference)
AG 181 179 1.06 (0.56‐2.00) 0.852
GG 11 6 1.93 (0.71‐5.23) 0.199
G vs A 1.11 (0.81‐1.52) 0.502
rs10055386
AA 358 342 1.00 (reference)
AG 387 409 0.94 (0.84‐1.06) 0.307
GG 155 149 1.03 (0.27‐4.01) 0.962
G vs A 1.02 (0.93‐1.11) 0.720
rs1482674
GG 547 558 1.00 (reference)
TG 287 282 1.08 (0.73‐1.6) 0.703
TT 56 50 1.19 (0.73‐1.94) 0.492
T vs G 1.1 (0.85‐1.42) 0.470
rs1839090
TT 258 262 1.00 (reference)
TG 433 421 1.09 (0.73‐1.61) 0.682
GG 209 217 1.02 (0.84‐1.23) 0.859
G vs T 1.03 (0.67‐1.58) 0.889
rs2290070
CC 631 629 1.00 (reference)
GC 247 253 1.01 (0.93‐1.1) 0.787
GG 22 18 1.27 (0.62‐2.61) 0.520
G vs C 1.05 (0.39‐2.79) 0.924
(Continues)
SUN ET AL. | 5

T A B L E 2 (Continued)

Genotype Myopia Controls Adjusted OR (95% CI)* P value

rs78454549
AA 599 612 1.00 (reference)
AG 271 261 1.1 (0.8‐1.52) 0.552
GG 30 27 1.18 (0.61‐2.29) 0.624
G vs A 1.1 (0.85‐1.44) 0.466
Abbreviations: BMI, body mass index; CI, confidence interval; FGF10, fibroblast growth factor 10; OR, odds ratio.
*Adjusted for age, sex, BMI, time spent outdoors, and time using electronic equipment.

3.4 | Genetic association study for 4 | DISCUSSION

FGF10 polymorphisms with high myopia
in young children In the current study, we evaluated 13 tagSNPs that
captured 100% of genetic variation in the FGF10 gene
We also evaluated the associations between 13 tagSNP of
region for their associations with myopia in a large
FGF10 and high myopia. As shown in Table 3, we found
Chinese case‐control study of young children. We found
rs339501 (OR: 1.73; 95% CI: 1.18‐2.53; P = 0.005),
rs2973644 was significantly associated with increased risk
rs2973644 (OR: 1.57; 95% CI: 1.13‐2.19; P = 0.007), and
of myopia. Besides, we also found rs339501, rs2973644,
rs79002828 (OR: 1.83; 95% CI: 1.20‐2.77; P = 0.005) were
and rs79002828 were significantly associated with an
significantly associated with increased risk of high
increased risk of high myopia in young children. FGF10
myopia in young children. Even adjusted for Bonferroni
plays essential roles in the development of myopia through
adjustment, our results were still significant.
modulating extracellular matrix‐associated genes.11 Func-
tional assessment of rs2973644 was performed by lucifer-
3.5 | Functional assessment of rs2973644 ase assays, and we found the risk G allele causes a higher
by luciferase assays expression level of FGF10 than the protective A allele.
Myopia is a multifactorial disease, and both genetic and
To validate that the A/G allele of SNP rs2973644 could
environmental factors are significant to its occurrence and
affect the FGF10 expression levels, two luciferase repor-
progression.7,14 Candidate gene approaches have been used
ters, carrying A or G allele, were constructed. As shown in
to explore the genetic architecture of myopia and some
Figure 2, the reporter carrying the G allele had a
possible susceptibility genes have been reported.13 His et al18
significantly higher expression level of luciferase activity
first evaluated eight SNPs in FGF10 and found rs339501 was
than the reporter carrying the A allele (P = 0.009). These
significantly associated with extreme myopia among Chinese
results suggested that the risk G allele causes a higher
Taiwan adults. Then, Yoshida et al19 replicated the findings
expression level than the protective A allele.
in Japanese adults and found rs339501, rs12517396, and

T A B L E 3 The associations between selected tagSNP of FGF10 and high myopia

Genotype High myopia Controls Adjusted OR (95% CI)* P value

rs339501
AA 65 681 1.00 (reference)
AG 31 209 1.62 (1.01‐2.58) 0.045
GG 4 10 4.36 (1.49‐12.75) 0.007
G vs A 1.73 (1.18‐2.53) 0.005
rs2973644
AA 45 520 1.00 (reference)
AG 44 328 1.61 (1.03‐2.53) 0.038
GG 10 52 2.31 (1.12‐4.78) 0.024
G vs A 1.57 (1.13‐2.19) 0.007
rs79002828
AA 71 737 1.00 (reference)
AG 25 154 1.75 (1.07‐2.88) 0.026
GG 3 9 3.60 (1.05‐12.31) 0.041
G vs A 1.83 (1.20‐2.77) 0.005
Abbreviations: BMI, body mass index; CI, confidence interval; FGF10, fibroblast growth factor 10; OR, odds ratio.
*Adjusted for age, sex, BMI, time spent outdoors, and time using electronic equipment.
6 |
F I G U R E 2 Functional assessment by luciferase reporter assay
for SNP rs2973644. Luciferase activity of the two constructs in the
RPE‐19 cell line. A significant difference of luciferase activities
between two reporter constructs (P = 0.009), using the data
(mean ± SEM) from three independent transfection experiments
rs10462070 (in complete linkage disequilibrium) were
associated with extreme myopia. However, the associations
of genetic variants of FGF10 with susceptibility of myopia in
young children, which are less affected by confounding
factors, and more suitable for studying genetic factors of
myopia, have not been explored. In the present study, we
first evaluated genetic variants of the FGF10 gene with
myopia and found rs2973644 was significantly associated
with increased risk of myopia. Further, we found rs339501,
rs2973644, and rs79002828 were significantly associated with
an increased risk of high myopia in young children.
Previously, Ren et al29 found that rs2973644 polymorphism
was significantly associated with susceptibility to chronic
obstructive pulmonary disease in a Han population of North
China. Our Functional assessment of rs2973644 by luciferase
assays revealed the risk G allele causes a higher expression
level of FGF10 than the protective A allele. Interestingly,
rs339501, which was located in the same intron of FGF10
with rs2973644, was previously identified to be involved in
the regulation of FGF10 gene expression.18 These findings
were consistent with that FGF10 gene regulation was
involved in the occurrence of myopia.
FGF10 gene is located in 5p12 and a member of the
FGF family. Studies of the mouse homolog suggested that
this gene is required for embryonic epidermal morpho-
genesis including brain development, lung morphogen-
esis, and initiation of limb bud formation.20 FGF10 is also
an oncogene that binds to FGFR2 and is overexpressed in
approximately 10% of human breast cancers.30 Very
recently, A new pathogenic variant in the FGF10 gene
was reported to be associated with lacrimal and salivary
gland syndrome.24 Besides, FGF10 is also involved in the
oncogenicity of pancreatic and breast cancers, and
variants in FGF10 are also potential risk factors for limb
deficiencies, cleft lip, and palate.31 All these findings
indicate that FGF10 is a crucial paracrine signal from the
mesenchyme to epithelium for development, health, and
disease.
SUN ET AL.
5 | CONCLUSIONS
We conducted a case‐control study of 13 tagSNPs among
900 myopia children and 900 nonmyopia children using a
candidate gene approach. Our results do support that
genetic variants of cytokine FGF10 are associated with
susceptibility of myopia (as well as high myopia) in
young children. Further studies in a larger population are
needed to verify these population‐specific findings.
ACKN OWLEDGMENT
We would like to thank all the subjects participating in
this project.
CON FLI C T OF I NT ER ES TS
The authors declared that there is conflict of interest.
RE FER E NCES
1. Chen M, Wu A, Zhang L, et al. The increasing prevalence of
myopia and high myopia among high school students in
Fenghua city, eastern China: a 15‐year population‐based
survey. BMC Ophthalmol. 2018;18:159.
2. Hagen LA, Gjelle JVB, Arnegard S, Pedersen HR, Gilson SJ,
Baraas RC. Prevalence and possible factors of myopia in
norwegian adolescents. Sci Rep. 2018;8:13479.
3. Huang YP, Singh A, Lai LJ. The prevalence and severity of
myopia among suburban schoolchildren in taiwan. Ann Acad
Med Singapore. 2018;47:253‐259.
4. Joseph S, Krishnan T, Ravindran RD, et al. Prevalence and risk
factors for myopia and other refractive errors in an adult
population in southern India. Ophthalmic Physiol Opt.
2018;38:346‐358.
5. Long E. Evolutionary medicine: why does prevalence of myopia
significantly increase? Evol Med Public Health. 2018;2018:151‐152.
6. Sun JT, An M, Yan XB, Li GH, Wang DB. Prevalence and
related factors for myopia in school‐aged children in qingdao.
J Ophthalmol. 2018;2018:9781987‐9781987.
7. Theophanous C, Modjtahedi BS, Batech M, Marlin DS, Luong
TQ, Fong DS. Myopia prevalence and risk factors in children.
Clin Ophthalmol. 2018;12:1581‐1587.
8. Wu L, Weng C, Xia F, Wang X, Zhou X. Internal astigmatism
and its role in the growth of axial length in school‐age children.
J Ophthalmol. 2018;2018:1686045‐1686045.
9. Hosaka A. Population studies—myopia experience in Japan.
Acta Ophthalmol Suppl. 1988;185:37‐40.
10. Hwang HS, Chun MY, Kim JS, Oh B, Yoo SH, Cho BJ. Risk
factors for high myopia in Koreans: The Korea National Health
and Nutrition Examination Survey. Curr Eye Res. 2018;43:
1052‐1060.
11. Pan CW, Qian DJ, Saw SM. Time outdoors, blood vitamin D status,
and myopia: a review. Photochem Photobiol Sci. 2017;16:426‐432.
12. Ramamurthy D, Lin Chua SY, Saw SM. A review of
environmental risk factors for myopia during early life,
SUN ET AL.
childhood, and adolescence. Clin Exp Optom. 2015;98:
497‐506.
13. Flitcroft DI, Loughman J, Wildsoet CF, Williams C, Guggen-
heim JA, Consortium C. Novel myopia genes and pathways
identified from syndromic forms of myopia. Invest Ophthalmol
Vis Sci. 2018;59:338‐348.
14. Jacobi FK, Zrenner E, Broghammer M, Pusch CM. A genetic
perspective on myopia. Cell Mol Life Sci. 2005;62:800‐808.
15. Siegwart JT, Jr., Norton TT. Perspective: how might emme-
tropization and genetic factors produce myopia in normal eyes?
Optom Vis Sci. 2011;88:E365‐E372.
16. Liew SH, Elsner H, Spector TD, Hammond CJ. The first
"classical" twin study? analysis of refractive error using
monozygotic and dizygotic twins published in 1922. Twin Res
Hum Genet. 2005;8:198‐200.
17. Tang SM, Lau T, Rong SS, et al. Vitamin D and its pathway
genes in myopia: systematic review and meta‐analysis. Br J
Ophthalmol. 2018;103:8‐17.
18. Hsi E, Chen KC, Chang WS, Yu ML, Liang CL, Juo SH. A
functional polymorphism at the FGF10 gene is associated with
extreme myopia. Invest Ophthalmol Vis Sci. 2013;54:3265‐3271.
19. Yoshida M, Meguro A, Okada E, Nomura N, Mizuki N.
Association study of fibroblast growth factor 10 (FGF10)
polymorphisms with susceptibility to extreme myopia in a
Japanese population. Mol Vis. 2013;19:2321‐2329.
20. Itoh N, Ohta H. Fgf10: a paracrine‐signaling molecule in
development, disease, and regenerative medicine. Curr Mol
Med. 2014;14:504‐509.
21. Curtain M, Heffner CS, Maddox DM, Gudis P, Donahue LR,
Murray SA. A novel allele of Alx4 results in reduced Fgf10
expression and failure of eyelid fusion in mice. Mamm Genome.
2015;26:173‐180.
22. Makarenkova HP, Ito M, Govindarajan V, et al. FGF10 is an
inducer and Pax6 a competence factor for lacrimal gland
development. Development. 2000;127:2563‐2572.
23. Puk O, Esposito I, Soker T, et al. A new Fgf10 mutation
in the mouse leads to atrophy of the harderian gland
and slit‐eye phenotype in heterozygotes: a novel model for
dry‐eye disease? Invest Ophthalmol Vis Sci. 2009;50:4311‐4318.
| 7
24. Rodrigo MJ, Idoipe M, Izquierdo S, et al. New pathogenic
variant in the FGF10 gene in the agenesis of lacrimal and
salivary gland syndrome: ophthalmological and genetic study.
Ophthalmic Genet. 2018;39:125‐128.
25. Tao H, Ono K, Kurose H, Noji S, Ohuchi H. Exogenous FGF10
can rescue an eye‐open at birth phenotype of Fgf10‐null mice
by activating activin and TGFalpha‐EGFR signaling. Dev
Growth Differ. 2006;48:339‐346.
26. Tsau C, Ito M, Gromova A, Hoffman MP, Meech R,
Makarenkova HP. Barx2 and Fgf10 regulate ocular glands
branching morphogenesis by controlling extracellular matrix
remodeling. Development. 2011;138:3307‐3317.
27. Luo HD, Gazzard G, Liang Y, Shankar A, Tan DT, Saw SM.
Defining myopia using refractive error and uncorrected
logMAR visual acuity > 0.3 from 1334 Singapore school
children ages 7‐9 years. Br J Ophthalmol. 2006;90:362‐366.
28. Tideman JW, Polling JR, Voortman T, et al. Low serum vitamin
D is associated with axial length and risk of myopia in young
children. Eur J Epidemiol. 2016;31:491‐499.
29. Ren JT, Feng K, Wang P, et al. Relationship between the gene
polymorphism in fibroblast growth factor‐10 and susceptibility
to chronic obstructive pulmonary disease 220 cases. Zhonghua
Jie He He Hu Xi Za Zhi. 2013;36:935‐939.
30. Ghoussaini M, French JD, Michailidou K, et al. Evidence that
the 5p12 Variant rs10941679 confers susceptibility to estrogen‐
receptor‐positive breast cancer through FGF10 and MRPS30
regulation. Am J Hum Genet. 2016;99:903‐911.
31. Itoh N. FGF10: A multifunctional mesenchymal‐epithelial
signaling growth factor in development, health, and disease.
Cytokine Growth Factor Rev. 2016;28:63‐69.
How to cite this article: Sun W, Li Y, Li J, et al.
Cytokine fibroblast growth factor 10 (FGF10)
polymorphisms are associated with risk of myopia
in young children. J Cell Biochem. 2019;1‐7.
https://doi.org/10.1002/jcb.28790